Article
Oncology
Yan Lan, Mahmoud Moustafa, Maximilian Knoll, Chunxiao Xu, Jennifer Furkel, Adam Lazorchak, Tsz-Lun Yeung, Sayed-Mohammad Hasheminasab, Molly Jenkins, Sarah Meister, Huakui Yu, Julian Schlegel, Bo Marelli, Zili Tang, Guozhong Qin, Carmen Klein, Jin Qi, Cheng Zhou, George Locke, Damir Krunic, Melissa Derner, Christian Schwager, Rachel Fontana, Katharina Kriegsmann, Feng Jiang, Katrin Rein, Mark Kriegsmann, Juergen Debus, Kin-Ming Lo, Amir Abdollahi
Summary: The combination of BA fusion protein with radiotherapy shows superior survival in murine tumor models, increasing tumor-infiltrating leukocytes, reprogramming the tumor microenvironment, and attenuating RT-induced fibrosis. This combination has the potential to eradicate therapy-resistant tumors while sparing normal tissue, supporting its clinical translation.
Review
Oncology
James L. Gulley, Jeffrey Schlom, Mary Helen Barcellos-Hoff, Xiao-Jing Wang, Joan Seoane, Francois Audhuy, Yan Lan, Isabelle Dussault, Aristidis Moustakas
Summary: Transforming growth factor-beta (TGF-beta) and programmed death-ligand 1 (PD-L1) have immunosuppressive functions in the tumor microenvironment (TME) and inhibiting these pathways can improve clinical outcomes and reduce toxicity.
MOLECULAR ONCOLOGY
(2022)
Review
Immunology
Tianye Li, Xinrun Wang, Mengke Niu, Mingli Wang, Jianwei Zhou, Kongming Wu, Ming Yi
Summary: The PD-1/PD-L1 signaling pathway is crucial in cancer immune evasion, and anti-PD-1/PD-L1 antibodies are a significant milestone in cancer immunotherapy. However, low response rates and therapeutic resistance remain obstacles. Studies have shown that overexpressed TGF-beta is an additional immunosuppressive factor. Blocking TGF-beta and PD-L1 simultaneously can enhance the efficacy of PD-L1 monoclonal antibodies and overcome resistance. Next-generation bispecific antibodies targeting TGF-beta and PD-L1 have demonstrated superior anti-tumor activity compared to anti-PD-1/PD-L1 monotherapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemical Research Methods
Yue A. Qi, Tapan K. Maity, Constance M. Cultraro, Vikram Misra, Xu Zhang, Catherine Ade, Shaojian Gao, David Milewski, Khoa D. Nguyen, Mohammad H. Ebrahimabadi, Ken-ichi Hanada, Javed Khan, Cenk Sahinalp, James C. Yang, Udayan Guha
Summary: The study identified potential immunogenic human leukocyte antigen (HLA) class I-presented peptides in melanoma and EGFR-mutant lung adenocarcinoma using large-scale proteogenomic profiling. This discovery could be valuable for developing precision immunotherapies.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Chemistry, Multidisciplinary
Wenwen Wang, Tinggan Yuan, Lili Ma, Yanjing Zhu, Jinxia Bao, Xiaofang Zhao, Yan Zhao, Yali Zong, Yani Zhang, Shuai Yang, Xinyao Qiu, Siyun Shen, Rui Wu, Tong Wu, Hongyang Wang, Dong Gao, Peng Wang, Lei Chen
Summary: This study developed a platform to assess T cell response for neoantigen screening and found that organoids preserved genetic features and similar neoantigen landscape of original tumors. The study also identified candidate neoantigen peptides with immunogenic potential and validated their antitumor activity, providing a practical strategy for neoantigen peptide identification in personalized immunotherapy.
Article
Multidisciplinary Sciences
Alessandra Castiglioni, Yagai Yang, Katherine Williams, Alvin Gogineni, Ryan S. Lane, Amber W. Wang, Justin A. Shyer, Zhe Zhang, Stephanie Mittman, Alan Gutierrez, Jillian L. Astarita, Minh Thai, Jeffrey Hung, Yeqing Angela Yang, Tony Pourmohamad, Patricia Himmels, Marco De Simone, Justin Elstrott, Aude-Helene Capietto, Rafael Cubas, Zora Modrusan, Wendy Sandoval, James Ziai, Stephen E. Gould, Wenxian Fu, Yulei Wang, James T. Koerber, Shomyseh Sanjabi, Ira Mellman, Shannon J. Turley, Soeren Mueller
Summary: Previous studies have shown that combining immune checkpoint inhibitors with TGFβ blockade enhances anti-tumor immune responses. In this study, the authors demonstrate that combining therapeutic anti-PD-L1 with anti-TGFβ treatment promotes expansion and differentiation of stem-cell like CD8+ T cells in an immune excluded preclinical tumor model. TGFβ signaling is associated with non-response to immune checkpoint blockade in patients with advanced cancers, particularly in the immune-excluded phenotype. The data suggest that TGFβ and PD-L1 work together to prevent expansion of stem cell-like CD8+ T cells and replacement of exhausted CD8+ T cells, thereby maintaining the T cell compartment in a dysfunctional state.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Ming Yi, Yuze Wu, Mengke Niu, Shuangli Zhu, Jing Zhang, Yongxiang Yan, Pengfei Zhou, Zhijun Dai, Kongming Wu
Summary: In this study, a bispecific antibody targeting TGF-beta and human PD-L1 was developed and showed strong antitumor effects in triple-negative breast cancer (TNBC). The bispecific antibody exhibited high binding affinity to its targets and effectively counteracted immunosuppressive signaling pathways. In vivo experiments demonstrated that the bispecific antibody had superior antitumor activity compared to monotherapies targeting the individual targets. The improved tumor microenvironment contributed to its potent antitumor effects. This study suggests that the bispecific antibody may be a promising agent for TNBC treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Steven H. Sun, Colin D. Angell, Himanshu Savardekar, Debasish Sundi, David Abood, Brooke Benner, Mallory J. DiVincenzo, Megan Duggan, Fouad Choueiry, Thomas Mace, Prashant Trikha, Gabriella Lapurga, Courtney Johnson, Erick J. Carlson, Catherine Chung, Blake R. Peterson, Jing Zhao, Kari L. Kendra, William E. Carson III
Summary: Inhibition of BTK activation reduces the activation of tumor-associated suppressor cells and improves the therapeutic response to anti-PD-L1 antibody, enhancing the immunotherapy of advanced melanoma.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Marlieke L. M. Jongsma, Antonius A. de Waard, Matthijs Raaben, Tao Zhang, Birol Cabukusta, Rene Platzer, Vincent A. Blomen, Anastasia Xagara, Tamara Verkerk, Sophie Bliss, Xiangrui Kong, Carolin Gerke, Lennert Janssen, Elmer Stickel, Stephanie Holst, Rosina Plomp, Arend Mulder, Soldano Ferrone, Frans H. J. Claas, Mirjam H. M. Heemskerk, Marieke Griffioen, Anne Halenius, Hermen Overkleeft, Johannes B. Huppa, Manfred Wuhrer, Thijn R. Brummelkamp, Jacques Neefjes, Robbert M. Spaapen
Summary: HLA class I glycoproteins play a crucial role in driving immune responses by presenting antigens, but tumors and pathogens often exploit this process for immune evasion. Through genome-wide screens, it was discovered that the cell surface glycosphingolipid repertoire determines effective HLA-I antigen presentation. Inhibition of GSL synthesis may represent a potential therapeutic target in cancer, infection, and autoimmunity, offering a promising avenue for immune modulation.
Article
Endocrinology & Metabolism
Therese Weider, Sarah J. Richardson, Noel G. Morgan, Trond H. Paulsen, Knut Dahl-Jorgensen, Sara Salehi Hammerstad
Summary: The study revealed that HLA class I expression is significantly upregulated in thyroid tissue from GD patients, along with a higher presence of enterovirus protein. Co-localization of STAT1 with HLA class I and PKR with VP1 within thyroid cells suggests an antiviral tissue response.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Oncology
X. M. Shao, J. Huang, N. Niknafs, A. Balan, C. Cherry, J. White, V. E. Velculescu, V Anagnostou, R. Karchin
Summary: The burden of HLA class II immunogenic mutations (IMMs) is associated with clinical responses to immune checkpoint blockade (ICB) in patients with melanoma and non-small-cell lung cancer (NSCLC). Patients with higher HLA class II IMM burden tend to have longer survival and show CD4+ T-cell infiltration and programmed death-ligand 1 expression. HLA class II IMMs play a distinct and complementary role in ICB responses compared to HLA class I.
ANNALS OF ONCOLOGY
(2022)
Article
Oncology
Jan-Malte Placke, Camille Soun, Jenny Bottek, Rudolf Herbst, Patrick Terheyden, Jochen Utikal, Claudia Pfoehler, Jens Ulrich, Alexander Kreuter, Christiane Pfeiffer, Peter Mohr, Ralf Gutzmer, Friedegund Meier, Edgar Dippel, Michael Weichenthal, Lisa Zimmer, Elisabeth Livingstone, Juergen C. Becker, Georg Lodde, Antje Sucker, Klaus Griewank, Susanne Horn, Eva Hadaschik, Alexander Roesch, Dirk Schadendorf, Daniel Robert Engel, Selma Ugurel
Summary: This study investigated the digitally quantified tumor PD-L1 expression for predicting the outcome of PD-1-based immune checkpoint blockade therapy. Results showed that patients with PD-L1-positive tumors had better response and prolonged progression-free survival and overall survival. Both digital and physician quantification of PD-L1 expression were independent predictors of survival in patients receiving PD-1-based ICB therapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Applied
Qian Wang, Hao Jiang, Hongli Zhang, Weiqiao Lu, Xiao Wang, Wenfeng Xu, Jia Li, Youjing Lv, Guoyun Li, Chao Cai, Guangli Yu
Summary: This study proposes a novel strategy of antibody-beta-glucan conjugates (AGC) to enhance the antitumor immune response to immune checkpoint blockade (ICB) therapy. AGC demonstrated powerful tumor suppression and promoted interaction between tumor cells and dendritic cells (DCs), thereby enhancing immunotherapeutic benefits.
CARBOHYDRATE POLYMERS
(2024)
Article
Biochemistry & Molecular Biology
Dieuwke L. Marvin, Jelmer Dijkstra, Rabia M. Zulfiqar, Michiel Vermeulen, Peter ten Dijke, Laila Ritsma
Summary: Melanoma patients with liver metastasis have a poor prognosis. The cytokine Transforming Growth Factor beta (TGF-beta) plays a role in melanoma cells and acts on cells in the liver. We hypothesized that this cytokine influences the metastatic outgrowth of melanoma in liver. To investigate this, we generated a model to turn on and off TGF-beta signaling in the B16F10 melanoma cells, and found that TGF-beta activation repressed cell growth and migration in vitro, while it increased outgrowth in liver in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Morten Nielsen, Mario Presti, Zsofia Sztupinszki, Agnete Witness Praest Jensen, Arianna Draghi, Christopher Aled Chamberlain, Aimilia Schina, Christina Westmose Yde, John Wojcik, Zoltan Szallasi, Michael Douglas Crowther, Inge Marie Svane, Marco Donia
Summary: This study investigated a melanoma patient resistant to anti-PD-1 treatment and found consecutive acquisition of B2M loss and impaired JAK1 signaling, leading to immune escape of tumor cells. These findings shed light on the complexity of acquired resistance to immunotherapy and suggest that coexisting altered pathways can result in pan T-cell immune escape.
CANCER IMMUNOLOGY RESEARCH
(2022)
Review
Oncology
Motonobu Saito, Koji Kono
Summary: Epstein-Barr virus-positive gastric cancer (EBV (+) GC) is a subtype of GC associated with EBV infection, exhibiting unique genomic and clinicopathological features compared to other subtypes. Noncoding RNAs derived from EBV-infected cells play crucial roles in oncogenesis and tumor progression in EBV (+) GC. Recent studies focus on genetic mutations and protein overexpression in EBV (+) GC, proposing potential targeted therapies for this subtype.
Article
Oncology
Takuro Matsumoto, Hirokazu Okayama, Shotaro Nakajima, Katsuharu Saito, Misato Ito, Akinao Kaneta, Yasuyuki Kanke, Hisashi Onozawa, Suguru Hayase, Shotaro Fujita, Wataru Sakamoto, Motonobu Saito, Zenichiro Seze, Tomoyuki Momma, Kosaku Mimura, Koji Kono
Summary: The study identified a set of 11 genes, including SH2D4A, that are downregulated during the adenoma-carcinoma sequence in MSS/CIN CRCs, mainly due to chromosome 8p deletions. The absence of SH2D4A was associated with poor prognosis and scarce T cell infiltration.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Yuta Endo, Takafumi Watanabe, Motonobu Saito, Katsuharu Saito, Rei Suzuki, Hideki Sano, Yutaka Natori, Eisaku Sasaki, Makiko Ueda, Norihito Kamo, Shigenori Furukawa, Shu Soeda, Koji Kono, Shigehira Saji, Keiya Fujimori
Summary: This case report describes a rare case of recurrent ovarian cancer with TPM3-NTRK1 gene fusion that was not responsive to Entrectinib treatment. Immunohistochemistry showed negative expression of TRK protein, suggesting the need for immunohistochemistry confirmation prior to Entrectinib administration.
MOLECULAR AND CLINICAL ONCOLOGY
(2022)
Article
Oncology
Akinao Kaneta, Shotaro Nakajima, Hirokazu Okayama, Takuro Matsumoto, Katsuharu Saito, Tomohiro Kikuchi, Eisei Endo, Misato Ito, Kosaku Mimura, Yasuyuki Kanke, Motonobu Saito, Zenichiro Saze, Shotaro Fujita, Wataru Sakamoto, Hisashi Onozawa, Tomoyuki Momma, Shinji Ohki, Koji Kono
Summary: This study found that the activation of the cGAS-STING pathway contributes to the recruitment of CD8(+) TILs in dMMR/MSI CRC.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Surgery
Leo Yamada, Motonobu Saito, Hiroya Suzuki, Shotaro Mochizuki, Eisei Endo, Koji Kase, Misato Ito, Hiroshi Nakano, Naoto Yamauchi, Takuro Matsumoto, Akinao Kaneta, Yasuyuki Kanke, Hisashi Onozawa, Hiroyuki Hanayama, Hirokazu Okayama, Shotaro Fujita, Wataru Sakamoto, Yohei Watanabe, Suguru Hayase, Zenichiro Saze, Tomoyuki Momma, Shinji Ohki, Koji Kono
Summary: This study aims to evaluate the clinical factors, including central venous catheter (CVC) placement and thromboprophylaxis approach, as well as retrosternal space's width as a predictive factor for upper extremity deep vein thrombosis (UEDVT) in patients receiving esophagectomy. The study concludes that the presence of CVC may not affect the development of UEDVT, but the preoperative evaluation of retrosternal ratio may predict the occurrence of UEDVT.
Article
Oncology
Hidekazu Shirota, Keigo Komine, Masanobu Takahashi, Shin Takahashi, Eisaku Miyauchi, Hidetaka Niizuma, Hiroshi Tada, Muneaki Shimada, Tetsuya Niihori, Yoko Aoki, Ikuko Sugiyama, Maako Kawamura, Jun Yasuda, Shuhei Suzuki, Takeshi Iwaya, Motonobu Saito, Tsuyoshi Saito, Hiroyuki Shibata, Toru Furukawa, Chikashi Ishioka
Summary: There has been a paradigm shift in cancer chemotherapy towards personalized medicine with molecular-targeted drugs. The Molecular Tumor Board (MTB) serves as a platform that integrates clinical and molecular features for clinical decisions. This study retrospectively analyzed cases discussed at the MTB, summarizing genetic alterations and treatment recommendations. The results provide valuable insights for simplifying treatment recommendations and improving personalized medicine accuracy.
Article
Oncology
Shotaro Nakajima, Kosaku Mimura, Akinao Kaneta, Katsuharu Saito, Masanori Katagata, Hirokazu Okayama, Motonobu Saito, Zenichiro Saze, Yohei Watanabe, Hiroyuki Hanayama, Takeshi Tada, Wataru Sakamoto, Tomoyuki Momma, Hiromasa Ohira, Koji Kono
Summary: This study investigated the role of tumor cell-intrinsic cGAS-STING in radiation-mediated remodeling of the tumor microenvironment (TME) in esophageal squamous cell carcinoma (ESCC). The findings demonstrate that cGAS-STING is involved in radiation-induced activation of immune cells and recruitment of tumor-promoting M2-tumor-associated macrophages (TAMs) through IL-34. Targeting IL-34 to block M2-TAM infiltration may improve the efficacy of radiation therapy and combination therapy with immune checkpoint inhibitors in ESCC.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2023)
Article
Oncology
Misato Ito, Kosaku Mimura, Shotaro Nakajima, Hirokazu Okayama, Katsuharu Saito, Takahiro Nakajima, Tomohiro Kikuchi, Hisashi Onozawa, Shotaro Fujita, Wataru Sakamoto, Motonobu Saito, Tomoyuki Momma, Zenichiro Saze, Koji Kono
Summary: This study found that the increased infiltration of M2 tumor-associated macrophages (M2-TAMs) in the colorectal cancer (CRC) tumor microenvironment (TME) is related to resistance against oxidative stress mediated by the Nrf2-HO-1 axis. The mRNA expression levels of antioxidant-related genes in M2-TAMs were positively correlated with the M2-TAM signature. Additionally, the expression levels of Nrf2 and HO-1 were significantly increased in M2-TAMs compared to other macrophage subsets.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Takahiro Sato, Motonobu Saito, Shotaro Nakajima, Katsuharu Saito, Masanori Katagata, Satoshi Fukai, Hirokazu Okayama, Wataru Sakamoto, Zenichiro Saze, Tomoyuki Momma, Kosaku Mimura, Koji Kono
Summary: Background: The PI3K/AKT signaling pathway is frequently activated in gastric cancer (GC), but AKT inhibitors are not effective in unselected GC patients. Methods: The effect of AKT inhibitors on cell viability was evaluated in ARID1A-deficient and ARID1A knockdown GC cells, as well as in HER2-positive and HER2-negative GC. Results: AKT inhibitors decreased the viability of ARID1A-deficient cells, with a greater effect in ARID1A-deficient/HER2-negative GC cells. Conclusion: AKT inhibitors show higher therapeutic efficacy in ARID1A-deficient/HER2-negative GC cells, suggesting targeted therapy using AKT inhibitors as a potential treatment strategy.
Article
Oncology
Shotaro Nakajima, Akinao Kaneta, Hirokazu Okayama, Katsuharu Saito, Tomohiro Kikuchi, Eisei Endo, Takuro Matsumoto, Satoshi Fukai, Mei Sakuma, Takahiro Sato, Kosaku Mimura, Motonobu Saito, Zenichiro Saze, Wataru Sakamoto, Hisashi Onozawa, Tomoyuki Momma, Koji Kono
Summary: The impact of tumor cell-intrinsic cGAS-STING pathway on immune cell infiltration and clinical outcomes in pMMR/MSS CRC has not been thoroughly investigated. Our study reveals the expression pattern of cGAS-STING in tumor cells and its effect on T cell infiltrations and clinical outcomes in pMMR/MSS CRC. These findings provide novel insights and therapeutic strategies for patients with pMMR/MSS CRC.
Article
Oncology
Mei Sakuma, Kosaku Mimura, Shotaro Nakajima, Akinao Kaneta, Tomohiro Kikuchi, Azuma Nirei, Takeshi Tada, Hiroyuki Hanayama, Hirokazu Okayama, Wataru Sakamoto, Motonobu Saito, Tomoyuki Momma, Zenichiro Saze, Koji Kono
Summary: To predict the efficacy of treatments for patients with esophageal squamous cell carcinoma (ESCC), T cell subpopulations were evaluated in ESCC patients treated with chemotherapy (CT), chemoradiotherapy (CRT), and nivolumab therapy (NT). The frequencies of PD-1(+) or TIM-3(+)CD4(+) T cells were significantly higher in cStage IV patients. PD-1(+)CD4(+) and TIM-3(+)CD8(+) T-cell populations were significantly higher in patients treated with CRT but were not associated with treatment response. The frequencies of CD4(+) and CD8(+) central memory T cells (T-CM) were significantly decreased during NT, suggesting a potential biomarker for therapeutic response prediction in ESCC patients.
Article
Medicine, General & Internal
Wataru Sakamoto, Yasuyuki Kanke, Hisashi Onozawa, Hirokazu Okayama, Hisahito Endo, Shotaro Fujita, Motonobu Saito, Zenichiro Saze, Tomoyuki Momma, Koji Kono
Summary: This study retrospectively evaluated the clinical short-term outcomes of neoadjuvant chemotherapy (NAC) using capecitabin and oxaliplatin for locally advanced rectal cancer. The study found that there were no severe adverse effects pre- or perioperatively, radical resection was achieved in all cases, and no cases of progressive disease were observed.
FUKUSHIMA JOURNAL OF MEDICAL SCIENCE
(2022)
Meeting Abstract
Oncology
Junko Suga, Motonobu Saito, Shigehira Saji
Article
Gastroenterology & Hepatology
Wataru Sakamoto, Shinji Ohki, Hisashi Onozawa, Hirokazu Okayama, Hisahito Endo, Shotaro Fujita, Motonobu Saito, Zenichiro Saze, Tomoyuki Momma, Seiichi Takenoshita, Koji Kono
Summary: The study found that in patients with advanced rectal cancer, there was no significant difference in overall survival, relapse-free survival, and local recurrence between those treated with SCRT and CRT, although CRT had a better histological therapeutic effect. Patients with LPNM had significantly poorer 5-year overall survival and relapse-free survival compared to those without LPNM.
JOURNAL OF THE ANUS RECTUM AND COLON
(2021)